Inflammation in anxiety.

Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX, USA. ssalim@uh.edu

Abstract

The idea of the existence of an interaction between the immune system and the central nervous system (CNS) has prompted extensive research interest into the subject of "Psychoneuroimmunology" taking the field to an interesting level where new hypotheses are being increasingly tested. Specifically, exactly how the cross talk of pathways and mechanisms enable immune system to influence our brain and behavior is a question of immense significance. Of particular relevance to this topic is the role of cytokines in regulating functions within the CNS that ultimately modulate behavior. Interestingly, psychological stress is reported to modulate cytokine production, suggesting potential relevance of this mediator to mental health. In fact, cytokine signaling in the brain is known to regulate important brain functions including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, as well as the neural circuitry of mood. It is rather obvious to expect an aberrant behavioral outcome as a result of a dysregulation in cytokine signaling which might lead to occurrence of depression, anxiety, and cognitive dysfunction. Thus, understanding the mechanisms by which the immune system influences behavior would reveal targets for potential therapeutic development as well as strategies for the prevention of neuropsychiatric diseases. To date, the presence of inflammatory responses and the crucial role of cytokines in depression have received most attention. However, considering a big socioeconomic impact due to an alarming increase in anxiety disorder patients, there is an urgent research need for a better understanding of the role of cytokines in anxiety. In this review, we discuss recent research on the role of neuroimmunology in anxiety. At the end, we offer an "oxidative stress theory," which we propose works perhaps as a "sensor of distress," the imbalance of which leads to neuroinflammation and causes anxiety disorders. Much research is needed to extensively test this theory keeping an open mind!